Abstract
In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the ‘Low lamin A expression’ group compared to patients from the ‘High lamin A expression’ group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A− carcinoma cells compared to lamin A+ carcinoma cells in patients from the ‘Low lamin A expression’ group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A− carcinoma cells in patients from the ‘High lamin A expression’ group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells.
Highlights
IntroductionThe microRNA-9 ( called miRNA-9 or miR-9) corresponding to the mature miR-9-5p is encoded by three genes in humans, namely, microRNA-9-1, microRNA-9-2, and microRNA-9-3, depending on their localization (chromosomes 1, 5, and 15, respectively)
The microRNA-9 corresponding to the mature miR-9-5p is encoded by three genes in humans, namely, microRNA-9-1, microRNA-9-2, and microRNA-9-3, depending on their localization
The downregulation of E-cadherin expression is associated with the epithelial to mesenchymal transition (EMT) and allows the dissociation of carcinomatous cells, promoting invasion and metastatic process [7,8,9,10]. miR-9 targets genes encoding tumor suppressor factors, such as FOXO1 (Forkhead box protein O1) and CDX2, increasing cell growth and proliferation, respectively, in breast and gastric cancer [11,12]. miR-9 directly targets SOX7 (SRY-Box 7), which is a transcription factor involved in developmental processes and acting as a tumor suppressor in several cancers
Summary
The microRNA-9 ( called miRNA-9 or miR-9) corresponding to the mature miR-9-5p is encoded by three genes in humans, namely, microRNA-9-1, microRNA-9-2, and microRNA-9-3, depending on their localization (chromosomes 1, 5, and 15, respectively). We postulated that low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis that is associated with EMT and could account for a pejorative factor correlated with a poor Performance status in lung adenocarcinoma [33]. In another context, the same expression pattern of A-type lamins has been previously described in neural cells. In this context, miR-9 could be a good candidate to explain the reduction of lamin A expression, as miR-9 seems to be a central actor in the carcinogenesis and the metastatic process of NSCLC, and it targets prelamin A mRNA, inhibiting the expression of lamin A but not of lamin C
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